Titre
Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Keshavjee, B.
Auteure/Auteur
Lambelet, V.
Auteure/Auteur
Coppola, H.
Auteure/Auteur
Viertl, D.
Auteure/Auteur
Prior, J.O.
Auteure/Auteur
Kappeler, L.
Auteure/Auteur
Armengaud, J.B.
Auteure/Auteur
Chouraqui, J.P.
Auteure/Auteur
Chehade, H.
Auteure/Auteur
Vanderriele, P.E.
Auteure/Auteur
Allouche, M.
Auteure/Auteur
Balsiger, A.
Auteure/Auteur
Sarre, A.
Auteure/Auteur
Peyter, A.C.
Auteure/Auteur
Simeoni, U.
Auteure/Auteur
Yzydorczyk, C.
Auteure/Auteur
Liens vers les unités
ISSN
2076-3921
Statut éditorial
Publié
Date de publication
2022-08-29
Volume
11
Numéro
9
Première page
1695
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Metabolic syndrome (MetS) refers to cardiometabolic risk factors, such as visceral obesity, dyslipidemia, hyperglycemia/insulin resistance, arterial hypertension and non-alcoholic fatty liver disease (NAFLD). Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing metabolic/hepatic disorders later in life. Oxidative stress and cellular senescence have been associated with MetS and are observed in infants born following IUGR. However, whether these mechanisms could be particularly associated with the development of NAFLD in these individuals is still unknown. IUGR was induced in rats by a maternal low-protein diet during gestation versus. a control (CTRL) diet. In six-month-old offspring, we observed an increased visceral fat mass, glucose intolerance, and hepatic alterations (increased transaminase levels, triglyceride and neutral lipid deposit) in male rats with induced IUGR compared with the CTRL males; no differences were found in females. In IUGR male livers, we identified some markers of stress-induced premature senescence (SIPS) (lipofuscin deposit, increased protein expression of p21 <sup>WAF</sup> , p16 <sup>INK4a</sup> and Acp53, but decreased pRb/Rb ratio, foxo-1 and sirtuin-1 protein and mRNA expression) associated with oxidative stress (higher superoxide anion levels, DNA damages, decreased Cu/Zn SOD, increased catalase protein expression, increased nfe2 and decreased keap1 mRNA expression). Impaired lipogenesis pathways (decreased pAMPK/AMPK ratio, increased pAKT/AKT ratio, SREBP1 and PPARγ protein expression) were also observed in IUGR male livers. At birth, no differences were observed in liver histology, markers of SIPS and oxidative stress between CTRL and IUGR males. These data demonstrate that the livers of IUGR males at adulthood display SIPS and impaired liver structure and function related to oxidative stress and allow the identification of specific therapeutic strategies to limit or prevent adverse consequences of IUGR, particularly metabolic and hepatic disorders.
PID Serval
serval:BIB_DA9451A3F95C
PMID
Open Access
Oui
Date de création
2022-10-04T09:28:56.116Z
Date de création dans IRIS
2025-05-21T04:09:43Z
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Nom
antioxidants-11-01695 (4).pdf
Version du manuscrit
preprint
Licence
https://creativecommons.org/licenses/by/4.0
Taille
7.85 MB
Format
Adobe PDF
PID Serval
serval:BIB_DA9451A3F95C.P001
URN
urn:nbn:ch:serval-BIB_DA9451A3F95C4
Somme de contrôle
(MD5):d8b8f72afbaf7eb3045003e272975288